Analyte measurement device and method of use

ABSTRACT

Devices, systems, methods and kits are provided for use in determining the concentration of chemical and biochemical components in aqueous fluids. The subject devices include test strips which define a longitudinal axis and include a distal edge configured for insertion into a measurement instrument and having an alignment notch formed in the distal edge for engagement with an alignment member of the measurement instrument. The alignment notch has opposing edges wherein at least a portion of the opposing edges is in substantially parallel relation to the longitudinal axis. In using the subject devices, the devices are inserted into a measurement instrument having an alignment pin. When operatively engaged with the alignment pin, the notch serves to maintain the device in a substantially motionless position. The invention is useful in a variety of applications, particularly in the determination of blood glucose concentrations.

FIELD OF THE INVENTION

[0001] The present invention is related to the field of medicaldiagnostic devices for determining the concentration of chemical andbiochemical components (analytes) in aqueous fluids. Particularly, thepresent invention is directed to measuring the concentration of ananalyte in, or a property of, a biological fluid such as blood and moreparticularly glucose in blood.

BACKGROUND OF THE INVENTION

[0002] The quantification or assay of chemical and/or biochemicalconstituents within biological fluids, such as blood, urine, and saliva,and within biological fluid fractions or derivatives such as blood serumand blood plasma, is of ever increasing importance for medical diagnosisand treatment, as well as the quantification of exposure to therapeuticdrugs, intoxicants, hazardous chemicals, and the like. One such commonapplication is the measurement of blood glucose levels in diabetics.

[0003] Widely accepted assays involve measuring a change in a physicalcharacteristic of the fluid being tested or an element of such fluidwhen exposed to a particular energy source. These physicalcharacteristics are typically an electrical, magnetic, fluidic, oroptical property of the fluid or a component thereof. For example, witha colorimetric assay system, an optical property may be monitoredwherein a change in light absorption of the fluid can be related to ananalyte concentration in, or a property of, the fluid.

[0004] To carry out the assays, a disposable test strip, pad, or thelike, is employed in conjunction with a meter. A sample of thebiological fluid to be tested is provided. When the biological fluid isblood, a sample is typically acquired by means of a finger stick. Thefluid sample is then deposited in a designated measurement area of thetest strip, which contains reagents selected for the particular assaybeing conducted. The test strip, or at least a portion thereof, isplaced in a receptacle area or test strip holder within the meter. Themeter is capable of receiving a signal originating in a measurement areaof the test strip and determining the existence and/or concentration ofthe constituent or analyte of interest. Examples of assay systems thatemploy these types of disposable test strips and meters may be found inU.S. application Ser. No. 09/333,765, filed Jun. 15, 1999, and Ser. No.09/356,248, filed Jul. 16, 1999; and in U.S. Pat. Nos. 4,935,346,5,049,487, 5,304,468 and 5,563,042, the disclosures of which are hereinincorporated by reference.

[0005] Often, the measurement area of the test strip is defined by asmall aperture within the surface of the test strip. Placed over andcovering the aperture on one side of the test strip is a hydrophilicmaterial, e.g., a membrane, matrix, layer, or the like, containingreagent(s) suitable for determining the existence and/or theconcentration of the particular analyte of interest. The sampled fluidis deposited on the opposite side of the test strip within the aperturewhereby the fluid is then absorbed into the hydrophilic matrix. Such atest strip configuration is used, for example, in calorimetricmeasurement systems; see, e.g., U.S. Pat. No. 5,563,042. Such systemsemploy meters, such as a diffuse reflectance spectrophotometer withaccompanying software, which can be made to automatically transmit alight source at a particular wavelength and then read reflectance, ofthe test sample at certain points in time, and, using calibrationfactors, determine the concentration of analyte in the sampled fluid.

[0006] In order to obtain an accurate measurement of the fluid sampledeposited within the aperture, it is necessary to properly position thetest strip within the test strip holder and aligned the aperture of thetest strip with the light source, typically a high-intensity lightemitting diode (LED), within the meter. Improper positioning of the teststrip can result, for example, from a slight rebound of the test stripas its distal or insertion end is caused to contact the edge of thestrip holder. Also, some shifting or slipping of the test strip mayoccur after it has been placed within the meter.

[0007] To facilitate proper positioning an alignment of the test stripwithin the test strip holder, a notch or a cut-out is formed within anedge of a test strip which is to be aligned with a corresponding ormating alignment pin within the inner edge of the test strip holder.This has not been completely successful as the strip is still able, tosome degree, to shift from side-to-side when the strip is not fullyinserted. Such movement or “play” in the position of the test stripincreases the likelihood that the test strip will be improperly or notcompletely inserted or misaligned within the meter. As a result of thismisalignment, the measurement aperture of the test strip may not becentered with respect to the light source, which may then result in anincorrect measurement.

[0008] Often, to compensate for this likelihood of misalignment and theresulting incorrect measurement, a larger aperture requiring a greatervolume of the biological fluid, e.g., blood, being tested is used so asto provide a larger measurement area within the test strip. Adisadvantage of using a greater volume of sampled fluid, blood inparticular, to saturate this area of exposed hydrophilic matrix, is theneed to draw a greater volume of blood sample from the patient. Thisrequisite greater volume of sampled fluid requires use of a blood samplesize which is rather large for a typical finger stick, thusnecessitating use of a larger diameter needle and/or deeper penetrationinto the skin. These factors can increase the discomfort and pain feltby the patient, and may be difficult to achieve for those individualswhose capillary blood does not readily express. As this sampling processmay be repeated frequently within a single day, for many diabetics, anincrease in pain quickly becomes less tolerable or intolerable alltogether.

[0009] As such, there is a continuing need for a test device for use inanalyte concentration measurement that is easy to insert into andself-aligning within a meter, highly resistant to rebounding uponinsertion and to movement once operatively placed within the meter, andminimizes the volume of the sample of biological fluid that is necessaryto ensure an accurate measurement.

[0010] Relevant Literature

[0011] Patents and publications of interest include: U.S. Pat. Nos.4,935,346, 5,049,487, 5,304,468 and 5,563,042.

SUMMARY OF THE INVENTION

[0012] The present invention is directed to fluid sampling and analytemeasurement devices, instrumentation, systems and kits, as well asmethods for using the same, which improve upon the prior art. Moreparticularly, test strips for holding a sampled fluid for measurement bya meter or an associated test strip holder are provided. The subjecttest strips may be provided in conjunction with a measurementinstrument, i.e., an analyte measurement meter, an analyte measurementsystem, a kit for analyte measurement and/or accessory devices.

[0013] The subject test devices are configured for insertion into ameasurement instrument or a test strip holder within a measurementinstrument. In many embodiments, the subject test strips are in the formof a thin, flat strip defining a longitudinal axis, and include a distaledge substantially transverse to the longitudinal axis and an alignmentnotch formed in the distal edge for engagement with an alignment memberor pin within the test strip holder of the meter or the meter itself.The alignment notch has opposing edges wherein at least a portion ofthese edges is substantially parallel to the longitudinal axis of thetest strip. The test devices further include an aperture for receiving avolume of a fluid sample that is less than that required by prior artdevices.

[0014] The subject test devices may include a support member and asample-absorbing member. The above-mentioned notch and aperture of thetest devices are features of the support member. Affixed to the bottomsurface of the support member is a sample-absorbing member in the formof a pad which covers the aperture. The pad is made of a hydrophilicmaterial and, as such, absorbs the fluid sample deposited on theaperture. A reagent material may be contained within the pad forfacilitating the measurement of the analyte targeted for measurement.

[0015] These and other features of the invention will become apparent tothose persons skilled in the art upon reading the details of the presentinvention as more fully described below.

BRIEF DESCRIPTIONS OF THE DRAWINGS

[0016]FIG. 1A is a top view of a schematic representation of a prior arttest strip in operative engagement with the alignment pin of a meter'stest strip holder (not shown);

[0017]FIG. 1B is perspective view of the prior art test strip of FIG.1A;

[0018]FIG. 2A is a top view of a schematic representation of the teststrip of the present invention in operative engagement with thealignment pin of a meter's test strip holder (not shown); and

[0019]FIG. 2B is enlarged view of the insertion end of the test strip ofFIG. 2A, illustrating the details of an optimized notch configurationand an optimized sample application aperture.

DETAILED DESCRIPTION OF THE INVENTION

[0020] Before the present invention is described in further detail, itis to be understood that this invention is not limited to the particularembodiment described, as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present invention will be limited onlyby the appended claims.

[0021] Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges is also encompassed within the invention, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either both ofthose included limits are also included in the invention.

[0022] Unless defined otherwise, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this invention belongs. Although any structureand method similar or equivalent to those described herein can also beused in the practice or testing of the present invention, the preferredstructure and method of use are now described. All publicationsmentioned herein are incorporated herein by reference to disclose anddescribe the structures and/or methods in connection with which thepublications are cited.

[0023] It must be noted that as used herein and in the appended claims,the singular forms “a”, “and”, and “the” include plural referents unlessthe context clearly dictates otherwise. Thus, for example, reference to“a test strip” includes a plurality of such test strips and reference to“the meter” includes reference to one or more meters and equivalentsthereof known to those skilled in the art, and so forth.

[0024] The publications discussed or cited herein are provided solelyfor their disclosure prior to the filing date of the presentapplication. Nothing herein is to be construed as an admission that thepresent invention is not entitled to antedate such publication by virtueof prior invention. Further, the dates of publication provided may bedifferent from the actual publication dates which may need to beindependently confirmed.

[0025] Overview

[0026] As summarized above, the subject invention provides an improvedtest strip for use with a measurement apparatus, e.g., an analytemeasuring meter, to determine the existence and/or concentration levelof analyte present in a sample of fluid. The subject test strip isparticularly suitable for use with a photometric instrument orspectrometer for the determination of the glucose concentration in asample of whole blood.

[0027] The advantages of the present invention will be better understoodin the context of the following comparison with the exemplary prior arttest strip of FIGS. 1A and 1B, and the description of an exemplaryembodiment of the test strip of the present invention as illustrated inFIGS. 2A and 2B.

[0028] Prior Art Teststrip(s)

[0029] Referring now to FIG. 1A, there is shown a top view of aschematic representation of one embodiment of a test strip 10 of theprior art operatively engaged with an alignment pin 20, commonlyprovided on the inside distal edge of a test strip holder (now shown) orwithin the inside distal edge of a test strip receiving area within themeter itself (not shown) for facilitating the alignment of test strip 10within a meter (not shown) for measurement of an analyte of interest.Such a test strip 10 is disclosed, for example, in U.S. Pat. No.5,563,042.

[0030] As is more clearly viewed in FIG. 1B, test strip 10 includes asupport member 12, typically made of a plastic material or the like, bywhich strip 10 can be held. Support member 12 has length and widthdimensions which are suitable for use with the test strip holder beingused. Typically, the length dimension is in the range from about 15 to60 mm, and the width dimension is in the range form about 5 to 20 mm.Mounted on either the top or bottom side of support member 12 is areagent element 11 in the form of a membrane, pad or the like, wherematrix pad 11 is typically made of a hydrophilic porous matrix and oneor more reagents impregnated into the pores of the matrix. The one ormore reagent(s) are selected based on the analyte targeted formeasurement and, in the case of photometric measurement, is capable ofreacting with the target analyte to produce a compound that ischaracteristically absorptive at a wavelength other than a wavelength atwhich the assay medium substantially absorbs light. Reagent element 11is directly and firmly attached to support member 12 by means of anon-reactive adhesive 13. Typically, the length dimension reagentelement 11 is in the range from about 5 to 20 mm, and the widthdimension is in the range form about 5 to 10 mm.

[0031] Aperture 14 is present in support member 12 in a portion of thearea to which reagent pad 11 is attached. Aperture 14 has a circularconfiguration having a diameter typically in the range from about 4.5 to5 mm. Accordingly, a typical surface area defined by circular aperture14 ranges from about 15.5 to 20 mm².

[0032] Support member 10 further comprises an alignment notch 15 in theform of a “V” at distal edge 17 and about the y-axis or verticalcenterline 18 (see FIG. 1A) of support member 12. More particularly,notch 15 consists of two straight segments 15 a, 15 b (one on each sideof vertical center line 18), each set at about a 45° angle with respectto vertical centerline 18 wherein the proximal ends of segments 15 a, 15b intersect at vertical centerline 18, forming the apex 15 c of notch15. The distal ends of legs 15 a, 15 b terminate, respectively, atpoints approximately between about 2 to 4 mm from the strip's verticalcenterline 18.

[0033] The measurement methodology using the above-described test strip10 involves the use of a measurement instrument or meter (not shown),such as a diffuse reflectance spectrophotometer having suitablesoftware, into which test strip 10 is operatively inserted. Generally, asuitable spectrophotometer includes a light source, such as one or morelight emitting diodes (LED), and a corresponding light reflectancedetector that can be adapted to respectively generate and respond tolight having a particular wavelength. Such meters are commonly known bythose skilled in the art of analyte measurement.

[0034] When operatively inserted into a test strip holder of a suitablemeter or a meter itself without a holder, test strip 10 is moved in aforward or distal direction until notch 15 is engaged with alignment pin20. The assay process begins by providing a sample containing theanalyte to be measured and applying it to aperture 14 of test strip 10.Application of the sample to aperture 14 may occur either prior to orafter insertion of test strip 10 into the test strip holder. Supportmember 12 holds reagent pad 11 so that a sample can be applied toaperture 14 on the top surface of support member 12 while lightreflectance is measured from the bottom surface of support member 12,i.e., on the side of the reagent pad 11 opposite aperture 14. Generally,the normal volume of sample applied is in the range from about 5 to 50μl and more typically from about 12 to 30 μl. A beam of light is thengenerated and projected onto the reagent pad 11 by a spectrophotometer,and the reflectance of the light created by the reaction between thereagent and the target analyte within the sample is then automaticallymeasured at certain times. The meter's software then automaticallycalculates the rate of change of reflectance between measurements, and,using calibration factors, determines the level of analyte in thesample.

[0035] The purpose of the alignment notch and alignment pin arrangementis to facilitate proper alignment of test strip 10 within the test stripholder such that aperture 14 is accurately aligned over the meter'slight source. Test strip 10 is allowed some movement about pin 20 atnotch 15 so that the side edges 16 of strip 10 will be properly seatedwithin the sides of the test strip holder (not shown). This is intendedto align aperture 14 over the light source within the measurement meter;however, it is this movement or lateral “play,” i.e., side-to-sideshifting, of test strip 10 that is often the cause of an improperlyaligned test strip.

[0036] Additionally, the V notch configuration has no means forspecifically preventing linear or longitudinal movement along the y-axis18 of test strip 10 once it is positioned within the test strip holder.To compensate for such movement, test strip 10 provides a large aperture14 requiring a greater volume of sample to be tested. Nonetheless, uponrebound, aperture 14 may be displaced enough such that none or aninsufficient amount of its interior surface area and the sampled fluidare aligned with the light source, resulting in an inaccuratemeasurement reading. Teststrip (s) of the Present Invention

[0037] Referring now to FIG. 2A, there is shown a top view of aschematic representation of a test device 30 of the present invention.In this embodiment, test device 30 is in the form of a flat, thinrectangular configuration, i.e., a test strip, defining a longitudinalaxis 38, however, it will be apparent to those of skill in the relevantart that other shapes and/or configurations are also contemplated bythis invention. Here, test strip device 30 is shown operatively engagedwith an alignment pin 40 of a test strip holder (not shown). Test strip30 has the same or similar general functions and construct as test strip10 of FIGS. 1A and 1B, and is compatible with the types of measurementinstruments mentioned herein.

[0038] Test strip 30 includes a support member 32 which is adhesivelyengaged on its bottom surface with a sample absorbing element 31. Here,support member 32 is illustrated having a rectangular configuration andsample-absorbing element 31 is in the form of a rectangular padpositioned with its longitudinal axis transverse to the longitudinalaxis of that of support member 32. Although such rectangularconfigurations are illustrated, any configuration compatible with agiven measuring instrument is acceptable for test strip 30. In manyembodiments, support member 32 is made of a plastic material including,but not limited to, polystyrene, polyester, polyethylene. Support member32 may also be made from other suitable materials including, laminates,paper and composites, such as recycled plastics. In many embodiments,sample-absorbing pad 31 is made of a hydrophilic matrix, typicallyporous, or another suitable matrix for the analyte(s) targeted formeasurement. The matrix oftentimes contains at least one reagentmaterial selected for such targeted analyte(s). Support member 32 andreagent pad 31 of test strip 30 may have length, width and thicknessdimensions which are the same as or similar to that of support member 12and reagent pad 11 of test strip 10 of FIGS. 1A and 1B. In certainembodiments, support member 32 has a length in the range from about 15to 60 mm, a width in the range from about 5 to 20 mm, and a thickness inthe range from about 0.1 to 2.5 mm. In many embodiments, reagent pad 31has a length in the range from about 5 to 20 mm, a width in the rangefrom about 5 to 10 mm, and a thickness in the range from about 0.05 to 1mm.

[0039] The geometry and dimensions of both aperture 34 and notch 35 haveconfigurations which advantageously optimize the use of test strip 30.More particularly, aperture 34 of test strip 30 has a non-circular shapeand a smaller surface area than aperture 14 of prior art test strip 10.In many embodiments, aperture 34 has a shape or configuration that issubstantially “obround” which comprises two halves of a circle extendedapart by a straight midsection. Other possible configurations ofaperture 34 include, but are not limited to, oval, elliptical or oblong,having a major axial length dimension that is coaxial with the y-axis orvertical centerline 38 of test strip 30. The obround geometry ofaperture 34 is more specifically defined by top and bottom half circlesor arcs 34 a and 34 b and midsection 36. Arcs 34 a and 34 b are eachdefined by a base width in the range from about 3 to 6 mm, moretypically in the range from about 3.5 to 4 mm, and by an arc height inthe range from about 1.5 to 3 mm, more typically in the range from about1.75 to 2 mm. Midsection 36 has the same width as the base width of arcs34 a and 34 b, and a height (along y-axis 38) in the range from about0.1 to 0.2 mm, and more typically about 0.15 mm. The total y-axistangent-to-tangent dimension for aperture 34 equals twice the arcdiameter plus the length of midsection 36 and, thus, is in the rangefrom about 3.1 to 6.2 mm, and more typically from about 3.5 to 4.5 mm.Accordingly, the surface area defined by aperture 34 is in the rangefrom about 7 to 30 mm², and more typically in the range from about 10 to13.5 mm². Certain embodiments of the test strips of the presentinvention have an aperture surface area preferably no greater than about15 mm²

[0040] As such, the volume of the fluid sample necessary to provide anaccurate measurement using test strip 30 of the present invention isless than that which is required when employing a prior art test strip.With the obround configuration of aperture 34, an amount of sample lessthan about 35 μl, and more typically less about 10 μl, and in certainembodiments, less than about 5 μl is required for an accuratemeasurement. Therefore, the volume of fluid sample, e.g., blood,necessary to be drawn from a patient is less than what is conventionallyrequired. Accordingly, relatively smaller needles, lancets and bloodletting devices or the like may be used for drawing the fluid samplefrom the patient or user of the device, thereby minimizing the pain anddiscomfort experienced by the patient during the sampling procedure, andminimizing the rate of non-compliance among patients.

[0041] As mentioned above, a test strip may have a tendency to springback or rebound in a proximal direction upon contact with the distal endof the test strip holder when being inserted into the test meter. Suchproximal displacement of the test strip, and of the measurementaperture, is such that the aperture's exposure, and thus the sampledfluid's exposure, to the light source beam of the meter is insufficientto provide an accurate measurement reading of the sample depositedwithin the aperture. However, with the obround configuration of aperture34, the shorter distance between apex 35 c to apex 40 of aperture 34,proximal displacement of test strip 30 within a nominal or typicaldistance will not limit the area of aperture 34 exposed to the lightsource beam. As such, the extended apex-to-apex distance minimizes theeffect of rebounding by test strip 30. Additionally, this featureprovides for an increased insertion zone such that a sufficient surfacearea of aperture 34 is exposed to the measurement source even when teststrip 30 is not fully inserted into the test strip holder or meter. Thisin turn facilitates a more accurate measurement of the sample and, overtime, maximizes the repeatability of accurate measurements.

[0042] Alignment notch 35 also has a shape and configuration differentfrom that of corresponding alignment notch 15 of prior art test strip10. FIG. 2B illustrates an exemplary configuration of notch 35. Notch 35has opposing edges, one on each side of centerline 38. Preferably, theopposing edges are the same, i.e., mirror images of each other, orsubstantially similar. At least a portion of the opposing edges of notch35 is in substantially parallel relation with each other and withcenterline 38. Notch 35 may also include one or more segment pairs in anangular relation with centerline 38.

[0043] In the exemplary embodiment of FIGS. 2A and 2B, notch 35 is shownhaving three pairs of opposing edge segments 35 a and 35 b, 35 a′ and 35b, and 35 a″ and 35 b″. However, notch 35 may have more or fewer segmentpairs, provided that the overall configuration of notch 35 providesstability to and substantially minimizes any shifting or movement oftest strip 30 when engaged within the meter.

[0044] Notch 35 consists of a first pair of edge segments 35 a, 35 b,one on each side of centerline 38, each set at an angle α with respectto centerline 38. Angle a preferably ranges from about 30° to 60°, andmore typically is about 45° from centerline 38. Segments 35 a, 35 b havelengths in the range from about 0.5 to 2.0 mm, and more typically in therange from about 0.7 to 1.25 mm. The respective distal ends of edgesegments 35 a, 35 b each extend laterally from centerline 38 a distancepreferably in the range from about 2.0 to 3.0 mm, and more typically inthe range from about 2.4 to 2.6 mm. The respective proximal ends of edgesegments 35 a, 35 b each extend inwardly from the respective distal endsand extend laterally from centerline 38 a distance preferably in therange from about 1.0 to 2.0 mm, and more typically in the range fromabout 1.5 to 1.7 mm.

[0045] The second pair of edge segments 35 a′ and 35 b′ extenddownwardly from the proximal ends of segments 35 a, 35 b, respectively,and are substantially parallel to centerline 38. Segments 35 a′,35 b′have lengths preferably distance preferably in the range from about 0.5to 2 mm, and more typically in the range from about 0.9 to 1.1 mm.

[0046] The third pair of segments 35 a″ and 35 b″ extend inwardly fromthe proximal ends of segments 35 a′, 35 b′, respectively, each formingan angle β with centerline 38. Angle β preferably ranges from about 30°to 60°, and more typically is about 45°. The proximal ends of segmentsof 35 a″ and 35 b″ intersect at centerline 38. Fillets with radii in therange from about 0.2 to 0.4 mm may be added at each of the segmentjunctures to facilitate the manufacturing process.

[0047] The configuration of alignment notch 35 overcomes many of thedisadvantages of previous notch designs. In particular, the second pairof segments 35 a′, 35 b′ of notch 35, i.e., the segments that aresubstantially parallel to centerline 38, act to guide test strip 30 in astraight insertion path into a test strip holder or meter upon operativeengagement between notch 35 and alignment pin 40. Furthermore, suchconfiguration of notch 35 acts to minimize the likelihood of lateralmovement of the test strip upon insertion into the test strip holder ormeter. Additionally, edge segments 35 a′,35 b′ maintain test strip 30 ina straight and optimally aligned position within the test strip holderor meter after insertion and during the testing process by restrictingany lateral movement of test strip 30.

[0048] System(S) of the Present Invention

[0049] The present invention also includes systems for measuring theconcentration of at least one target analyte in a biological fluidsample. The subject systems include at least one of the subject teststrips and a measurement instrument. The measurement instrument may beany instrument adapted and suitable for measuring a targeted analyte ina fluid sample, including a physiological or biological fluid sample,such as interstitial fluid, blood, blood fractions, and the like. Thetest strips are particularly suitable for use with an optical orphotometric device (e.g., a spectrometer), but the test strips mayinclude components for use with an electrochemical measurementinstrument without departing from the scope of the invention.

[0050] The measurement meter typically includes a test strip holder intowhich the test strip is directly inserted, but the meter need not havesuch a holder. In either case, the meter has an alignment pin, either inthe strip holder or a test strip receptacle area of the meter. Thealignment notch of the subject test strips has a configuration forengagement with the alignment pin to ensure proper alignment of the teststrip upon insertion. Additionally, this notch-pin engagement maintainsthe test strip in a substantially motionless position with respect tothe alignment pin when said test strip is operatively engaged within thetest strip holder or meter, as described above.

[0051] Methods of using the Test Strip(s) of the Present Invention

[0052] An exemplary method of the subject invention involves using atleast one subject test device in conjunction with a measurementinstrument for measuring the concentration of at least one constituentin a fluid sample. Also provided by the subject invention are methods ofusing the subject devices, i.e., the test strips, to determine theexistence and concentration of chemical and biochemical components(analytes) in aqueous fluids. A variety of different constituents, e.g.,analytes, may be detected and their concentrations may be determinedusing the subject test strips, where representative constituents includeglucose, cholesterol, lactate, alcohol, and the like. In manyembodiments, the subject methods are employed to determine the glucoseconcentration in an aqueous fluid, e.g., a biological fluid. While inprinciple the subject methods may be used to determine the concentrationof a constituent in a variety of different biological samples, such asurine, tears, saliva, and the like, they are particularly suited for usein detecting and determining the concentration of a constituent in bloodor blood fractions and more particularly whole blood.

[0053] In practicing the subject methods, the first step is to provide atest device, e.g., a test strip or the like, defining a longitudinalaxis and having a distal edge which is substantially transverse to thelongitudinal axis, an aperture for receiving the fluid sample, asdescribed above, and an alignment notch formed in the distal edge forengagement with an alignment member of a measurement instrument, e.g., apin of a test strip holder or a pin in the receptacle area of a meter,wherein such an alignment notch has opposing edges where at least aportion of the opposing edges is in substantially parallel relation tothe longitudinal axis.

[0054] Either prior to or after insertion of the subject test strip intoa suitable measuring instrument, a quantity of the biological sample isthen applied or introduced to the test strip, i.e., to the aperture ofthe test strip. The amount of biological sample, e.g., blood, that isapplied to the test strip may vary, but is generally less than about 5μl. The sample may be applied to the test strip using any convenientprotocol, where the sample may be injected, wicked, and the like. Inmany embodiments, e.g., colorimetric assays, the sample is allowed toreact with the reagent(s) of the test strip to produce a detectableproduct, as described above.

[0055] Automated meters for measuring the concentration of at least oneof the constituents in a biological sample deposited on the test stripfor use with calorimetric assays are well known in the art, for examplesee U.S. Pat. No. 5,059,395, the disclosure of which is hereinincorporated by reference. The measurement instrument includes analignment pin configured for engagement with the alignment notch of thetest strip. As mentioned above, the meter may include a test stripholder into which the test strip is directly inserted, but the meterneed not have such a holder. In either case, the meter includes thealignment pin, either in a test strip holder or in the meter itself,e.g., in a test strip receptacle area of the meter. Accordingly, uponinsertion of the test strip into the meter, the test strip, and morespecifically the alignment notch of the test strip, is operativelyengaged with the alignment pin of the measuring instrument.Specifically, the alignment pin of the measurement instrument isoperatively engaged between the opposing parallel edges of the teststrip. In many embodiments, the test strip is maintained in asubstantially motionless position while it is operatively engaged withthe alignment pin. In other words, undesirable, unintended or unwantedmovement or displacement of the test strip, lateral movement inparticular, while the test strip is engaged with the alignment pin issubstantially hindered, minimized or all together prevented due to theengagement of the notch and pin.

[0056] In certain embodiments, the subject methods further includeminimizing the effect of any proximal displacement of the test strip, ifsuch proximal displacement should occur. Accordingly, in manyembodiments, the effect of proximal displacement is minimized byincreasing the insertion zone or area of the test strip, as describedabove. For example, in certain embodiments, the insertion zone isincreased by extending or lengthening the depth of the alignment notch,as described above in reference to FIG. 2A (i.e., the distance betweenthe alignment notch apex and the distal edges of the test strip isincreased over the prior art) such that test device aperture ispositioned closer to the distal boundary of the meter or the test stripholder. As such, the aperture is more likely to remain within themeasurement area, i.e., the area in which the meter's light source istargeted, if such rebounding or proximal displacement (within a nominalor typical range) of test device does occur. In other embodiments, theinsertion zone is increased by decreasing the insertion gap, asdescribed above. Regardless of the way in which the insertion zone isincreased, the result of such increase minimizes the effect of anyproximal displacement the test strip may have.

[0057] Following insertion and operative engagement of the test stripwithin the measurement instrument, measurements are made. Morespecifically, the detectable product produced by the interaction of thebiological sample and at least one reagent of the test strip is detectedand related to the amount of constituent, e.g., analyte, in the sampleby the measurement instrument.

[0058] Additionally, the subject methods may further include repeatingthe above-described method for a plurality of measurements of one ormore samples of fluid, wherein the measurement results are more accurateand have better repeatability over the prior art.

[0059] Kits

[0060] Also provided by the subject invention are kits for use inpracticing the subject methods. The kits of the subject inventioninclude at least one subject test device or test strip. The kits mayalso include a measurement instrumentation that may be used withreusable or disposable test devices. Certain kits may include varioustest devices or test strips having different sizes and/or containing thesame or different reagents. Additionally, the kits many include certainaccessories such as a means for sampling the fluid to be tested. Forexample, the means for sampling may include, but is not limited to, aneedle, lancet or blood letting device for drawing from less than about5 μl to about 10 μl of blood from a patient. Finally, the kitspreferably include instructions for using the subject devices andinstrumentation in the determination of an analyte concentration in afluid sample. The instructions for use may include, for example,language instructing the user of the kit to apply less than about 35 μl,less than about 10 μl, or less than about 5 μl of the fluid sample tothe test device. These instructions may be present on one or more of thepackaging, a label insert, or containers present in the kits, and thelike.

[0061] It is evident from the above description that the features of thesubject test strip overcome many of the disadvantages of prior art teststrips including, but not limited to, minimizing the movement of thetest strip during and after insertion within a test strip holder,minimizing the detrimental effects of rebound and a lack of fullinsertion of the test strip if such should occur, and decreasing thevolume of fluid sample needed for an accurate measurement. Otheradvantages of the subject test strip are the reduction in painexperienced by a patient as a result of requiring a lower sample volumeand ensuring greater repeatability in the measurement process. As such,the subject invention represents a significant contribution to thefield.

[0062] The subject invention is shown and described herein in what isconsidered to be the most practical, and preferred embodiments. It isrecognized, however, that departures may be made there from, which arewithin the scope of the invention, and that obvious modifications willoccur to one skilled in the art upon reading this disclosure.

[0063] Although the present invention is useful for many applications,the sampling of various fluids and the detection of many types ofconstituents, the invention has been described primarily in the contextof the detection of analytes in biological fluid, and as beingparticularly useful for the detection of glucose in blood. Thus, thespecific devices and methods disclosed and the applications, biologicalfluids and constituents discussed herein are considered to beillustrative and not restrictive. Modifications that come within themeaning and range of equivalents of the disclosed concepts, such asthose that would readily occur to one skilled in the relevant art, areintended to be included within the scope of the appended claims.

That which is claimed is:
 1. A test device for insertion into ameasurement instrument having an alignment member therein for engagementwith said test device, said test device comprising: (a) a longitudinalaxis; (b) a distal edge substantially transverse to said longitudinalaxis and configured for insertion into said measurement instrument; and(c) an alignment notch formed in said distal edge for engagement withsaid alignment member and comprising opposing edges wherein at least aportion of said opposing edges is in substantially parallel relation tosaid longitudinal axis.
 2. The test device of claim 1 further comprisingan aperture therein for receiving a volume of a fluid sample therein,wherein said volume is less than about 35 μL.
 3. The test device ofclaim 2 wherein said volume is less than about 10 μL.
 4. The test deviceof claim 3 wherein volume is less than about 5 μL.
 5. The test device ofclaim 2 wherein said aperture has a non-circular configuration.
 6. Thetest device of claim 5 wherein said aperture has an obroundconfiguration.
 7. The method according to claim 2 wherein said aperturehas a surface area no greater than about 15 mm².
 8. The test device ofclaim 2 further comprising a support member and a sample-absorbingmember, wherein said longitudinal axis, said distal edge, said notch andsaid aperture are features of said support member, said support memberfurther comprising a top surface and a bottom surface wherein saidaperture extends from said top surface to said bottom surface, andwherein said sample-absorbing member is fixed to said top or bottomsurface of said support member and covers said aperture.
 9. The testdevice of claim 8 wherein said sample-absorbing member comprises ahydrophilic material.
 10. The test device of claim 9 wherein saidhydrophilic material is porous.
 11. The test device of claim 9 whereinsaid sample-absorbing member comprises at least one reagent materialselected for reacting with at least one constituent of said volume offluid sample.
 12. The test device of claim 11 wherein said fluid sampleis blood and said constituent is glucose.
 13. A test strip for use inconjunction with a measurement instrument having an alignment membertherein and for measuring the concentration of at least one analytewithin a sample of biological fluid, said test strip comprising: (a) asupport member defining a longitudinal axis and comprising: (i) a distaledge substantially transverse to said longitudinal axis and configuredfor insertion into said measurement instrument; (ii) an alignment notchformed in said distal edge for engagement with said alignment member andcomprising opposing edges wherein at least a portion of said opposingedges is in substantially parallel relation to said longitudinal axis;and (iii) an aperture therein for receiving said sample of biologicalfluid; and (b) a reagent pad fixed to said support member and coveringsaid aperture, said reagent pad containing at least one reagent materialselected for reacting with said at least one analyte.
 14. The test stripof claim 13 wherein at least a portion of said opposing edges is inangular relation to said longitudinal axis.
 15. The test strip of claim14 wherein said opposing edges comprises at least three portions whereintwo of the three portions of said opposing edges are in angular relationto said longitudinal axis.
 16. The test strip of claim 14 wherein saidportion of said opposing edges in substantially parallel relation islocated in between said two portions of said opposing edges in angularrelation to said longitudinal axis.
 17. A system for measuring theconcentration of at least one target analyte in a sample of biologicalfluid, said system comprising: (a) at least one test strip having topand bottom surfaces, comprising: (i) a substantially obround-shapedaperture for receiving a volume of from less than about 5 μl to about 10μl of said sample of biological fluid; (ii) a hydrophilic pad affixed toone of said top or bottom surfaces and covering said substantiallyobround-shaped aperture; and (iii) an alignment notch comprisingopposing parallel edges; and (b) a measurement instrument comprising analignment pin configured for engagement with said alignment notchwherein said test strip is maintained in a substantially motionlessposition with respect to said alignment pin when said test strip isoperatively engaged within said test strip holder.
 18. The system ofclaim 17 wherein said volume of said sample is less than about 5 μl. 19.The system of claim 17 wherein said measurement instrument is aspectrometer.
 20. A method of measuring the concentration of at leastone constituent in a fluid sample, the method comprising the steps of:(a) providing a test device defining a longitudinal axis and comprising:(i) a distal edge substantially transverse to said longitudinal axis;(ii) an alignment notch formed in said distal edge for engagement withan alignment pin of a measurement instrument adapted for measuring theconcentration of said at least one constituent in said fluid sample,said alignment notch comprising opposing edges wherein at least aportion of said opposing edges is in substantially parallel relation tosaid longitudinal axis; and (iii) an aperture formed therein forreceiving said fluid sample; (b) inserting said test device into saidmeasurement instrument; and (c) operatively engaging said alignmentnotch with said alignment pin.
 21. The method of claim 20 furthercomprising the step of maintaining said test device in a substantiallymotionless position while said test strip is operatively engaged withsaid alignment pin.
 22. The method of claim 20 further comprising thestep of minimizing the effect of any proximal displacement experiencedby said test strip upon insertion into said measurement instrument. 23.The method of claim 22 wherein the step of minimizing the effectcomprises the step of increasing the insertion zone of said test strip.24. The method of claim 20 further comprising the step of applying fromabout less than 5 to 35 μl of said fluid sample to said aperture.
 25. Akit for measuring the concentration of at least one constituent in afluid sample, said kit comprising at least one test device defining alongitudinal axis and comprising: (a) a distal edge substantiallytransverse to said longitudinal axis; (b) an alignment notch formed insaid distal edge for engagement with said alignment member andcomprising opposing edges wherein at least a portion of said opposingedges is in substantially parallel relation to said longitudinal axis;and (c) an aperture formed therein for receiving said fluid sample. 26.The kit according to claim 25 wherein said aperture has a substantiallyobround configuration.
 27. The kit according to claim 25 furthercomprising a fluid sample-absorbing member affixed to said at least onetest device and covering said aperture.
 28. The kit according to claim25 further comprising instructions for using said kit.
 29. The kitaccording to claim 28 wherein said instructions of using instruct a userof said kit to apply from less than about 5 to about 35 μl of fluidsample to said aperture.
 30. The kit according to claim 29 wherein saidinstructions of using instruct a user of said kit to apply from lessthan about 5 to about 10 μl of fluid sample to said aperture.
 31. Thekit according to claim 30 wherein said instructions of using instruct auser of said kit to apply less than about 5 μl of fluid sample to saidaperture.